|郭紘志老師為本會會員，任職於中央研究院細胞與個體生物學研究所，其研究專注於環狀RNA與反式剪接RNA在維持全能性、再編程與調控分化的功能探討。郭老師實驗室最近於自然通訊期刊(Nature Communications)發表了一篇有關環狀RNA circBIRC6參與控制人類胚胎幹細胞多能性分子迴路的重要論文，感謝郭老師跟我們分享其成果如下:|
|The circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency|
Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are important research tools that allow us to study the mechanisms underlying cellular differentiation and self-renewal along with differentiated tissue development and regeneration in vitro. PSCs also provide the basis for the field of regenerative medicine and offer hope for the treatment of a wide range of human conditions that can be attributed to the loss or malfunction of specific cell types.
CircRNAs are one types of Non-colinear transcripts, which joins exons within a single pre-mRNA, thereby forming circular RNAs in which the exon order is a circular permutation of that encoded by the genomic sequence. Although it is evident that large numbers of circRNAs exist in the human transcriptome, and accumulating evidence suggests that they may play important roles in regulating cellular function, the role of circRNA in human PSCs and the mechanism by which circRNAs regulate pluripotency and early-lineage differentiation has not been previously described.
In the past years, we have focused our efforts on characterizing the functional role of circRNA and the mechanism by which they regulate pluripotency and/or differentiation machinery as well as transcription factor-mediated pluripotency reprogramming. Here, we identified a subset of circRNAs that are enriched in hESCs and demonstrated that two circRNAs are functionally associated with the pluripotent state. Mechanistically, we found that circBIRC6 was enriched in AGO2 complexes and suppressed miR-34a and miR-145-mediated differentiation by directly interacting with these miRNAs. Our data thus suggest that circBIRC6 functions as a miRNA sponge to attenuate miRNA-mediated activity. Our study also demonstrates that ESRP1, a hESC-enriched splicing factor, promotes circBIRC6 synthesis through interactions with its flanking introns. Furthermore, we found that the expression of ESRP1 is regulated by NANOG and OCT4 in hESCs. Our study suggests the existence of a regulatory network in hESCs, wherein coordinated interactions between pluripotency-associated transcription factors and splicing factors modulate the expression of a distinct group of circRNAs, which can directly interact with miRNAs and influence the state of pluripotency.
The Full article is available at https://www.nature.com/articles/s41467-017-01216-w
The website of Dr. Kuo’s lab at http://icob.sinica.edu.tw/lab.php?id=31